[Show abstract][Hide abstract] ABSTRACT: Background:
The circulation of human adenovirus type 21 (HAdV21) in the United States has been documented since the 1960s in association with outbreaks of febrile respiratory illness (FRI) in military boot camps and civilian cases of respiratory disease.
To describe the molecular epidemiology of HAdV21 respiratory infections across the country, 150 clinical respiratory isolates obtained from continuous surveillance of military recruit FRI, and 23 respiratory isolates recovered from pediatric and adult civilian cases of acute respiratory infection were characterized to compile molecular typing data spanning 37 years (1978-2014).
Restriction enzyme analysis and genomic sequencing identified 2 clusters of closely related genomic variants readily distinguishable from the prototype and designated 21a-like and 21b-like. A-like variants predominated until 1999. A shift to b-like variants was noticeable by 2007 after a 7-year period (2000-2006) of cocirculation of the 2 genome types. US strains are phylogenetically more closely related to European and Asian strains isolated over the last 4 decades than to the Saudi Arabian prototype strain AV-1645 isolated in 1956.
Knowledge of circulating HAdV21 variants and their epidemic behavior will be of significant value to local and global FRI surveillance efforts.
The Journal of Infectious Diseases 03/2015; 212(6). DOI:10.1093/infdis/jiv141 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Streptococcus pneumoniae infections have periodically caused significant morbidity and outbreaks among military personnel, especially trainees. This study evaluated the effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in reducing pneumonia in healthy military trainees.
From 2000-2003, 152723 military trainees from 5 US training camps were enrolled in a double-blind, placebo-controlled trial of PPV23. Participants were closely monitored during basic training for radiographically confirmed pneumonia etiology and loss-of-training days. Participants were also followed using electronic medical encounter data until 1 June 2007 for three additional outcomes: any-cause pneumonia, any acute respiratory disease, and meningitis.
Comparison of demographic data by study arm suggested the randomization procedures were sound. During basic training, 371 study participants developed radiographically confirmed pneumonia. None had evidence of S. pneumoniae infection, but other etiologies included adenovirus (38%), Chlamydophila pneumoniae (9%), and Mycoplasma pneumoniae (8%). During the follow-up period, many study participants, in both the vaccine and placebo groups, had clinical encounters for the medical outcomes of interest. However, Cox's proportional hazard modeling revealed no evidence of a protective vaccine effect during recruit training (radiographically confirmed pneumonia) or up to 6.7 years after enrollment (any-cause pneumonia, any acute respiratory disease, or meningitis).
Data from this large, double-blind, placebo controlled trial do not support routine use of PPV23 among healthy new military trainees. This clinical trial was registered at clinicaltrials.gov (registration number NCT02079701, http://www.clinicaltrials.gov/ct2/show/NCT02079701?term=NCT02079701&rank=1).
[Show abstract][Hide abstract] ABSTRACT: Electronic event-based biosurveillance systems (EEBS's) that use near real-time information from the internet are an increasingly important source of epidemiologic intelligence. However, there has not been a systematic assessment of EEBS evaluations, which could identify key uncertainties about current systems and guide EEBS development to most effectively exploit web-based information for biosurveillance. To conduct this assessment, we searched PubMed and Google Scholar to identify peer-reviewed evaluations of EEBS's. We included EEBS's that use publicly available internet information sources, cover events that are relevant to human health, and have global scope. To assess the publications using a common framework, we constructed a list of 17 EEBS attributes from published guidelines for evaluating health surveillance systems. We identified 11 EEBS's and 20 evaluations of these EEBS's. The number of published evaluations per EEBS ranged from 1 (Gen-Db, GODsN, MiTAP) to 8 (GPHIN, HealthMap). The median number of evaluation variables assessed per EEBS was 8 (range, 3-15). Ten published evaluations contained quantitative assessments of at least one key variable. No evaluations examined usefulness by identifying specific public health decisions, actions, or outcomes resulting from EEBS outputs. Future EEBS assessments should identify and discuss critical indicators of public health utility, especially the impact of EEBS's on public health response.
PLoS ONE 10/2014; 9(10):e111222. DOI:10.1371/journal.pone.0111222 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
In late 2011, after a 12-year hiatus, oral vaccines against adenovirus types 4 (Ad4) and 7 (Ad7) were again produced and administered to US military recruits. This study examined the impact of the new adenovirus vaccines on febrile respiratory illness (FRI) and adenovirus rates and investigated if new serotypes emerged. FRI rates and their associated hospitalizations had markedly risen since vaccine production ceased in 1999.
From 1996 to 2013, the Naval Health Research Center conducted FRI surveillance at 8 military recruit training centers in the United States. During this period, 58 103 FRI pharyngeal swab specimens were studied, yielding 37 048 adenovirus-positive cases, among which 64% were typed.
During the 2 years after reintroduction of the vaccines, military trainees experienced a 100-fold decline in adenovirus disease burden (from 5.8 to 0.02 cases per 1000 person-weeks, P < .0001), without evidence that vaccine pressure had increased the impact of adenovirus types other than Ad4 and Ad7. Although the percentage of type 14 increased following reintroduction of the vaccination, the actual number of cases decreased. We estimate that the vaccines prevent approximately 1 death, 1100-2700 hospitalizations, and 13 000 febrile adenovirus cases each year among the trainees.
These data strongly support the continued production and use of Ad4 and Ad7 vaccines in controlling FRI among US military trainees. Continued surveillance for emerging adenovirus subtypes is warranted.
[Show abstract][Hide abstract] ABSTRACT: Adenovirus (ADV) types 4 (ADV-4) and 7 (ADV-7) are presently the major cause of febrile acute respiratory disease (ARD) in U.S. military recruits. We conducted a multi-center, randomized, double-blind, placebo-controlled phase 3 study of the new vaccine to assess its safety and efficacy. Healthy adults at two basic training sites were randomly assigned to receive either vaccine (two enteric-coated tablets consisting of no less than 4.5log10 TCID50 of live ADV-4 or ADV-7) or placebo in a 3:1 ratio. Volunteers were observed throughout the approximate eight weeks of their basic training and also returned for four scheduled visits. The primary endpoints were prevention of febrile ARD due to ADV-4 and seroconversion of neutralizing serum antibodies to ADV-7, which was not expected to circulate in the study population during the course of the trial. A total of 4151 volunteers were enrolled and 4040 (97%) were randomized and included in the primary analysis (110 were removed prior to randomization and one was removed after randomization due to inability to swallow tablets). A total of 49 ADV-4 febrile ARD cases were identified with 48 in the placebo group and 1 in the vaccine group (attack rates of 4.76% and 0.03%, respectively). Vaccine efficacy was 99.3% (95% CI, 96.0-99.9; P<0.001). Seroconversion rates for vaccine recipients for ADV-4 and ADV-7 were 94.5% (95% CI, 93.4-95.5%) and 93.8% (95% CI: 93.4-95.2%), respectively. The vaccine was well tolerated as compared to placebo. We conclude that the new live, oral ADV-4 and ADV-7 vaccine is safe and effective for use in groups represented by the study population.
[Show abstract][Hide abstract] ABSTRACT: In its 15th year, the Global Emerging Infections Surveillance and Response System (GEIS) continued to make significant contributions to global public health and emerging infectious disease surveillance worldwide. As a division of the US Department of Defense's Armed Forces Health Surveillance Center since 2008, GEIS coordinated a network of surveillance and response activities through collaborations with 33 partners in 76 countries. The GEIS was involved in 73 outbreak responses in fiscal year 2011. Significant laboratory capacity-building initiatives were undertaken with 53 foreign health, agriculture and/or defense ministries, as well as with other US government entities and international institutions, including support for numerous national influenza centers. Equally important, a variety of epidemiologic training endeavors reached over 4,500 individuals in 96 countries. Collectively, these activities enhanced the ability of partner countries and the US military to make decisions about biological threats and design programs to protect global public health as well as global health security.
[Show abstract][Hide abstract] ABSTRACT: Following the 2009 influenza A/H1N1 (pH1N1) pandemic, both seasonal and pH1N1 viruses circulated in the US during the 2010-2011 influenza season; influenza vaccine effectiveness (VE) may vary between live attenuated (LAIV) and trivalent inactivated (TIV) vaccines as well as by virus subtype.
Vaccine type and virus subtype-specific VE were determined for US military active component personnel for the period of September 1, 2010 through April 30, 2011. Laboratory-confirmed influenza-related medical encounters were compared to matched individuals with a non-respiratory illness (healthy controls), and unmatched individuals who experienced a non-influenza respiratory illness (test-negative controls). Odds ratios (OR) and VE estimates were calculated overall, by vaccine type and influenza subtype.
A total of 603 influenza cases were identified. Overall VE was relatively low and similar regardless of whether healthy controls (VE = 26%, 95% CI: -1 to 45) or test-negative controls (VE = 29%, 95% CI: -6 to 53) were used as comparison groups. Using test-negative controls, vaccine type-specific VE was found to be higher for TIV (53%, 95% CI: 25 to 71) than for LAIV (VE = -13%, 95% CI: -77 to 27). Influenza subtype-specific analyses revealed moderate protection against A/H3 (VE = 58%, 95% CI: 21 to 78), but not against A/H1 (VE = -38%, 95% CI: -211 to 39) or B (VE = 34%, 95% CI: -122 to 80).
Overall, a low level of protection against clinically-apparent, laboratory-confirmed, influenza was found for the 2010-11 seasonal influenza vaccines. TIV immunization was associated with higher protection than LAIV, however, no protection against A/H1 was noted, despite inclusion of a pandemic influenza strain as a vaccine component for two consecutive years. Vaccine virus mismatch or lower immunogenicity may have contributed to these findings and deserve further examination in controlled studies. Continued assessment of VE in military personnel is essential in order to better inform vaccination policy decisions.
PLoS ONE 07/2012; 7(7):e41435. DOI:10.1371/journal.pone.0041435 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge of spatial patterns of dengue virus (DENV) infection is important for understanding transmission dynamics and guiding effective disease prevention strategies. Because movement of infected humans and mosquito vectors plays a role in the spread and persistence of virus, spatial dimensions of transmission can range from small household foci to large community clusters. Current understanding is limited because past analyses emphasized clinically apparent illness and did not account for the potentially large proportion of inapparent infections. In this study we analyzed both clinically apparent and overall infections to determine the extent of clustering among human DENV infections.
We conducted spatial analyses at global and local scales, using acute case and seroconversion data from a prospective longitudinal cohort in Iquitos, Peru, from 1999-2003. Our study began during a period of interepidemic DENV-1 and DENV-2 transmission and transitioned to epidemic DENV-3 transmission. Infection status was determined by seroconversion based on plaque neutralization testing of sequential blood samples taken at approximately six-month intervals, with date of infection assigned as the middate between paired samples. Each year was divided into three distinct seasonal periods of DENV transmission. Spatial heterogeneity was detected in baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence calculated by trimester from 2001-2003 was spatially similar to preexisting DENV-1 and DENV-2 seroprevalence. Global clustering (case-control Ripley's K statistic) appeared at radii of ∼200-800 m. Local analyses (Kuldorf spatial scan statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999-2003. The number of seroconversions per cluster ranged from 3-34 with radii from zero (a single household) to 750 m; 65% of clusters had radii >100 m. No clustering was detected among clinically apparent infections.
Seroprevalence of previously circulating DENV serotypes can be a predictor of transmission risk for a different invading serotype and, thus, identify targets for strategically placed surveillance and intervention. Seroprevalence of a specific serotype is also important, but does not preclude other contributing factors, such as mosquito density, in determining where transmission of that virus will occur. Regardless of the epidemiological context or virus serotype, human movement appears to be an important factor in defining the spatial dimensions of DENV transmission and, thus, should be considered in the design and evaluation of surveillance and intervention strategies.
[Show abstract][Hide abstract] ABSTRACT: Recent clusters of outbreaks of mosquito-borne diseases (Rift Valley fever and chikungunya) in Africa and parts of the Indian Ocean islands illustrate how interannual climate variability influences the changing risk patterns of disease outbreaks. Although Rift Valley fever outbreaks have been known to follow periods of above-normal rainfall, the timing of the outbreak events has largely been unknown. Similarly, there is inadequate knowledge on climate drivers of chikungunya outbreaks. We analyze a variety of climate and satellite-derived vegetation measurements to explain the coupling between patterns of climate variability and disease outbreaks of Rift Valley fever and chikungunya.
We derived a teleconnections map by correlating long-term monthly global precipitation data with the NINO3.4 sea surface temperature (SST) anomaly index. This map identifies regional hot-spots where rainfall variability may have an influence on the ecology of vector borne disease. Among the regions are Eastern and Southern Africa where outbreaks of chikungunya and Rift Valley fever occurred 2004-2009. Chikungunya and Rift Valley fever case locations were mapped to corresponding climate data anomalies to understand associations between specific anomaly patterns in ecological and climate variables and disease outbreak patterns through space and time. From these maps we explored associations among Rift Valley fever disease occurrence locations and cumulative rainfall and vegetation index anomalies. We illustrated the time lag between the driving climate conditions and the timing of the first case of Rift Valley fever. Results showed that reported outbreaks of Rift Valley fever occurred after ∼3-4 months of sustained above-normal rainfall and associated green-up in vegetation, conditions ideal for Rift Valley fever mosquito vectors. For chikungunya we explored associations among surface air temperature, precipitation anomalies, and chikungunya outbreak locations. We found that chikungunya outbreaks occurred under conditions of anomalously high temperatures and drought over Eastern Africa. However, in Southeast Asia, chikungunya outbreaks were negatively correlated (p<0.05) with drought conditions, but positively correlated with warmer-than-normal temperatures and rainfall.
Extremes in climate conditions forced by the El Niño/Southern Oscillation (ENSO) lead to severe droughts or floods, ideal ecological conditions for disease vectors to emerge, and may result in epizootics and epidemics of Rift Valley fever and chikungunya. However, the immune status of livestock (Rift Valley fever) and human (chikungunya) populations is a factor that is largely unknown but very likely plays a role in the spatial-temporal patterns of these disease outbreaks. As the frequency and severity of extremes in climate increase, the potential for globalization of vectors and disease is likely to accelerate. Understanding the underlying patterns of global and regional climate variability and their impacts on ecological drivers of vector-borne diseases is critical in long-range planning of appropriate disease and disease-vector response, control, and mitigation strategies.
[Show abstract][Hide abstract] ABSTRACT: Since 2004, the Naval Health Research Center, with San Diego and Imperial counties, has collaborated with the US Centers for Disease Control and Prevention to conduct respiratory disease surveillance in the US-Mexico border region. In 2007, the Secretariat of Health, Mexico and the Institute of Public Health of Baja California joined the collaboration.
The identification of circulating respiratory pathogens in respiratory specimens from patients with influenza-like illness (ILI).
Demographic, symptom information and respiratory swabs were collected from enrollees who met the case definition for ILI. Specimens underwent PCR testing and culture in virology and bacteriology.
From 2004 through 2009, 1855 persons were sampled. Overall, 36% of the participants had a pathogen identified. The most frequent pathogen was influenza (25%), with those aged 6-15 years the most frequently affected. In April 2009, a young female participant from Imperial County, California, was among the first documented cases of 2009 H1N1. Additional pathogens included influenza B, adenovirus, parainfluenza virus, respiratory syncytial virus, enterovirus, herpes simplex virus, Streptococcus pneumoniae, and Streptococcus pyogenes.
The US-Mexico border is one of the busiest in the world, with a large number of daily crossings. Due to its traffic, this area is an ideal location for surveillance sites. We identified a pathogen in 36% of the specimens tested, with influenza A the most common pathogen. A number of other viral and bacterial respiratory pathogens were identified. An understanding of the incidence of respiratory pathogens in border populations is useful for development of regional vaccination and disease prevention responses.
Influenza and Other Respiratory Viruses 12/2011; 6(5):358-66. DOI:10.1111/j.1750-2659.2011.00316.x · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory illnesses can cause substantial morbidity during military deployments. Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, adenovirus, parainfluenza, and respiratory syncytial virus (RSV) are hypothesized causes.
To determine pathogen-specific seroprevalence prior to and after deployment in support of Operation Enduring Freedom (OEF).
A retrospective cohort study of 1000 service members deployed between June 30, 2004, and June 30, 2007, was conducted from 2008 through 2009. Pre- and post-deployment sera were tested for the presence of antibody to each pathogen.
Pre-deployment IgG seropositivity was high for adenovirus, RSV, and parainfluenza (98.7%, 97.8%, and 81.6%, respectively), whereas seropositivity for B. pertussis, M. pneumoniae, and C. pneumoniae was 14.2%, 21.9%, and 65.1%, respectively. As defined by seroconversion in 1000 subjects, the following were identified: 43 new parainfluenza infections (24% of susceptibles); 37 new pertussis infections (4% of susceptibles); 33 new C. pneumoniae infections (10% of susceptibles); and 29 new M. pneumoniae infections (4% of susceptibles). B. pertussis seroconversion was two to four times higher than reports for the general U.S. population. Overall, 14.2% of the service members seroconverted to at least one of these six pathogens; this increased to 30.1% seroconversion when influenza was included. However, serologic testing was not clearly associated with clinical illness in this report.
Serologic evidence for respiratory infections was common among the 2004-2007 OEF-deployed military, sometimes at a higher rate than the general U.S. population. Awareness of this risk and implementation of preventive measures should be emphasized by leadership prior to and during deployment.
American journal of preventive medicine 12/2011; 41(6):573-80. DOI:10.1016/j.amepre.2011.08.006 · 4.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The likely extended absence of an approved and cost-effective group A streptococcal (GAS) vaccine means both primary and secondary prophylaxis for GAS infections will largely remain dependent on the widely recommended BPG. Additionally, published data confirm reduced eradication efficacy of GAS from the throat following BPG administration. Further concern is the possible effect of a recent change in BPG manufacturers in the US. We therefore measured serum PCN-G levels during a 4 week period after BPG administration.
Methods: Military consented basic trainees received 1,200,000 units of intramuscular BPG (Monarch/Pfizer Pharmaceuticals). Sera were obtained on staggered days from each subject 3 times during the 4 week follow-up. Serum samples were analyzed (blinded) by liquid chromatography/mass spectrometry analysis controlling for study cohort, BPG lot number, and body size (M2).
Results: 329 subjects [two cohorts (n=164 and 165)] were enrolled. Mean age was 20 years. Mean body weight was 75 kg. Serum PCN-G levels were <0.03, <0.02 and <0.01 µg/ml by days 9, 11 and 15 respectively. 50% of subjects had [serum] <0.03, <0.02 and <0.01 µg/ml by days 6, 9 and 16 respectively. There were no significant differences associated with cohort, BPG lot number, or body size. The half-life for serum PCN-G was 4.1 days.
Conclusion: In active young adults serum PCN-G levels were well below published (0.012, 0.016 µg/ml)and currently accepted PCN-G MIC90 values in less than 2.5 weeks. These data, along with recently published results reporting that currently recommended doses of BPG are associated with almost 40% failure to eradicate GAS from the throat, require serious reconsideration for future medical and public health recommendations/guidelines for GAS treatment and secondary prophylaxis for GAS infections in older adolescents/adults. Additional studies are needed in children and also for therapy of syphilis/yaws in adults.
Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
[Show abstract][Hide abstract] ABSTRACT: When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3-4 weeks serum penicillin G levels are less than adequate (below MIC(90) of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections.
PLoS ONE 10/2011; 6(10):e25308. DOI:10.1371/journal.pone.0025308 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oropouche (ORO) virus, a member of the Simbu serogroup, is one of the few human pathogens in the Orthobunyavirus genus in the family Bunyaviridae. Genetic analyses of ORO-like strains from Iquitos, Peru, identified a novel reassortant containing the S and L segments of ORO virus and the M segment of a novel Simbu serogroup virus. This new pathogen, which we named Iquitos (IQT) virus, was first isolated during 1999 from a febrile patient in Iquitos, an Amazonian city in Peru. Subsequently, the virus was identified as the cause of outbreaks of "Oropouche fever" during 2005 and 2006 in Iquitos. In addition to the identification of 17 isolates of IQT virus between 1999 and 2006, surveys for neutralizing antibody among Iquitos residents revealed prevalence rates of 14.9% for ORO virus and 15.4% for IQT virus. Limited studies indicate that prior infection with ORO virus does not seem to protect against disease caused with the IQT virus infection. Identification of a new Orthobunyavirus human pathogen in the Amazon region of Peru highlights the need for strengthening surveillance activities and laboratory capabilities, and investigating the emergence of new pathogens in tropical regions of South America.
[Show abstract][Hide abstract] ABSTRACT: The Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) has the mission of performing surveillance for emerging infectious diseases that could affect the United States (U.S.) military. This mission is accomplished by orchestrating a global portfolio of surveillance projects, capacity-building efforts, outbreak investigations and training exercises. In 2009, this portfolio involved 39 funded partners, impacting 92 countries. This article discusses the current biosurveillance landscape, programmatic details of organization and implementation, and key contributions to force health protection and global public health in 2009.
BMC Public Health 03/2011; 11 Suppl 2(Suppl 2):S2. DOI:10.1186/1471-2458-11-S2-S2 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Armed Forces Health Surveillance Center's Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supports and oversees surveillance for emerging infectious diseases, including respiratory diseases, of importance to the U.S. Department of Defense (DoD). AFHSC-GEIS accomplishes this mission by providing funding and oversight to a global network of partners for respiratory disease surveillance. This report details the system's surveillance activities during 2009, with a focus on efforts in responding to the novel H1N1 Influenza A (A/H1N1) pandemic and contributions to global public health. Active surveillance networks established by AFHSC-GEIS partners resulted in the initial detection of novel A/H1N1 influenza in the U.S. and several other countries, and viruses isolated from these activities were used as seed strains for the 2009 pandemic influenza vaccine. Partners also provided diagnostic laboratory training and capacity building to host nations to assist with the novel A/H1N1 pandemic global response, adapted a Food and Drug Administration-approved assay for use on a ruggedized polymerase chain reaction platform for diagnosing novel A/H1N1 in remote settings, and provided estimates of seasonal vaccine effectiveness against novel A/H1N1 illness. Regular reporting of the system's worldwide surveillance findings to the global public health community enabled leaders to make informed decisions on disease mitigation measures and controls for the 2009 A/H1N1 influenza pandemic. AFHSC-GEIS's support of a global network contributes to DoD's force health protection, while supporting global public health.
BMC Public Health 03/2011; 11 Suppl 2(Suppl 2):S6. DOI:10.1186/1471-2458-11-S2-S6 · 2.26 Impact Factor